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It's the bacterial toxins that cripple cells in infections, study finds infrastructure

Columbus Daily Reporter - 5/8/2018

An Ohio State University-led study on a bacterial toxin linked to cholera and raw-oyster poisoning found that the toxin shuts down multiple, essential cell functions at once.

The discovery could one day open the door to exploring better ways to fight life-threatening infections, lead researchers Elena Kudryashova and Dmitri Kudryashov of The Ohio State University said in a press release.

The study focused on the bacterial toxin called ACD modifies an abundant cellular protein called actin and converts it into a secondary toxin. Actin plays a part in human processes, such as muscle contraction, cell division, cellular communication and immune response.

"You can think of actin like the bones and the muscles of the cell - and a barrier to what comes into and out of the cell," said Kudryashov, an associate professor of chemistry and biochemistry at Ohio State. "It's clearly beneficial for bacteria to paralyze it in some way and we now think we know how that happens for one actin-specific toxin."

Published in Current Biology, the researchers wanted to better understand how a relatively small amount of bacterial toxin could do such swift, significant damage to a strong network of actin.

"This is basically like crippling a nation by disabling all its instructors: Political and military leadership, teachers and others," Kudryashov said. "The population (actin) is there, but without proper instructions most transportation, imports and exports, border protection and other normal activities are halted or disorganized all at once."

Researchers believe the work is important in light of growing concerns about antibiotic-resistant infections.

"The bacteria are becoming 'smarter,' and so we must become much smarter as well," said Kudryashova, a research scientist in chemistry and biochemistry at Ohio State.

The research team's previous work found his particular bacterial toxin goes after the abundant actin proteins as opposed to the more-expected targeting of less-common molecules that send important cellular signals, according to a press release.

The lead researchers were joined by other Ohio State scientists for the study - David Heisler, a former graduate student who is the co-lead author of the study, as well as former undergraduate students Blake Williams and Kyle Shafer.

The National Institutes of Health supported this research.